Summary information and primary citation
- PDB-id
-
9gd7;
DSSR-derived features in text and
JSON formats
- Class
- DNA binding protein
- Method
- cryo-EM (4.25 Å)
- Summary
- DNA-pk ku80 mediated dimer bound to DNA polymerase
lambda and DNA ligase 4-xrcc4
- Reference
-
Frit P, Amin H, Zahid S, Barboule N, Hall C, Matharu G,
Hardwick SW, Chauvat J, Britton S, Chirgadze DY, Ropars
V, Charbonnier JB, Calsou P, Chaplin AK (2025): "Structural
and functional insights into the interaction between
Ku70/80 and Pol X family polymerases in NHEJ."
Nat Commun, 16, 4208. doi:
10.1038/s41467-025-59133-2.
- Abstract
- Non-homologous end joining (NHEJ) is the main repair
pathway for double-strand DNA breaks (DSBs) in mammals. DNA
polymerases lambda (Pol λ) and mu (Pol μ), members of the
Pol X family, play a key role in this process. However,
their interaction within the NHEJ complexes is unclear.
Here, we present cryo-EM structures of Pol λ in complex
with the DNA-PK long-range synaptic complex, and Pol μ
bound to Ku70/80-DNA. These structures identify interaction
sites between Ku70/80 and Pol X BRCT domains. Using mutants
at the proteins interface in functional assays including
cell transfection with an original gap-filling reporter, we
define the role of the BRCT domain in the recruitment and
activity of the two Pol X members in NHEJ and in their
contribution to cell survival following DSBs. Finally, we
propose a unified model for the interaction of all Pol X
members with Ku70/80.
